Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study

Abstract

Our aim was to assess the ability of tocilizumab monotherapy to reduce progressive structural joint damage in rheumatoid arthritis patients at high risk of progression. This study was a subanalysis from a prospective 1-year, multicenter, X-ray-reader-blinded, randomized controlled trial of tocilizumab [Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 Inhibitor (SAMURAI) trial]. All patients were categorized into two or three groups according to four independent predictive markers for progressive joint damage [urinary C-terminal crosslinking telopeptide (uCTX-II), urinary pyridinoline/deoxypyridinoline (uPYD/DPD) ratio, body mass index (BMI), and joint-space narrowing (JSN) score at baseline]. One-year progression of joint destruction was assessed in high-risk versus low-risk groups receiving tocilizumab monotherapy and compared with patients receiving conventional disease-modifying antirheumatic drugs (DMARDs) (n = 157 and 145, respectively). In patients at high risk of progression of erosion as estimated by high uCTX-II, uPYD/DPD, or low BMI, and at high risk of progression of JSN as estimated by low BMI or high JSN score, the 52-week changes in radiological erosion and JSN, respectively, were significantly less in patients treated with tocilizumab monotherapy compared with those receiving DMARDs for each type of risk factor. In patients at low risk, those receiving tocilizumab also progressed less than those on DMARDs, although the difference did not reach statistical significance. Tocilizumab monotherapy is more effective in reducing radiological progression in patients presenting with risk factors for rapid progression than in low-risk patients. Patients at high risk for progression may benefit more from tocilizumab treatment.

Fig. 1

One-year change of erosion scores in tocilizumab-treated rheumatoid arthritis (RA) patients at high risk for developing erosions. One-year change in erosion scores were analyzed for individual risk factors (a uCTX, b uPYD/DPD, c BMI) at baseline. Results are expressed as median (line across boxes), 25–75% interquartile range (boxes), mean (cross symbol in boxes), standard deviation (SD) (vertical line across the top of the box), and standard error (vertical line across bottom of the box). The filled circles represent individual values over SD values. Differences in changes in erosion scores were compared by the Wilcoxon rank sum test. uPYD/DPD urinary pyridinoline/deoxypyridinoline ratio, uCTX-II urinary C-terminal telopeptide of type II collagen, BMI body mass index, TCZ tocilizumab

Fig. 2

One-year change of joint space narrowing (JSN) scores in tocilizumab-treated rheumatoid arthritis (RA) patients with risk factors for developing JSN. Score changes were analyzed for individual risk factors (a uCTX, b uPYD/DPD, c BMI, d JSN) at baseline. Results are expressed as median (line across boxes), 25–75% interquartile range (boxes), mean (cross symbol in boxes), standard deviation (SD) (vertical line across top of the box), and standard error (vertical line across bottom of the box). The filled circles represent individual values over SD values. Differences in change in JSN scores were compared by the Wilcoxon rank sum test. uPYD/DPD urinary pyridinoline/deoxypyridinoline ratio, uCTX-II urinary C-terminal telopeptide of type II collagen, BMI body mass index, TCZ tocilizumab